207920Orig1s000 - Food and Drug Administration · 207920Orig1s000 OTHER REVIEW(S) Labeling Review for ... The October 23, 2015 labeling review discusses the February 6 and July 31,

CENTER FOR DRUG EVALUATION AND RESEARCH

APPLICATION NUMBER:

207920Orig1s000

OTHER REVIEW(S)

Labeling Review for Nexium24HR

Delayed-Release Tablets Draft Labeling

SUBMISSION DATES: November 17, 2015 NDA/SUBMISSION TYPE: 207920 ACTIVE INGREDIENTS: Esomeprazole 20 mg DOSAGE FORM Delayed-release tablet SPONSOR: Pfizer, Inc.

Christine Chirdo Director, U.S. Regulatory Strategy Category Lead 973-660-5602

REVIEWER: Mary R. Vienna, RN, MHA, DNDP, ODE IV TEAM LEADER: Steven Adah, Ph.D., DNDP, ODE IV ASSOCIATE DIRECTOR for LABELING REGULATORY PROJECT MANAGER

Ruth E. Scroggs, PharmD, DNDP, ODE IV Jung Lee, PharmD, Project Manager, DNDP, ODE IV

I. BACKGROUND AstraZeneca LP (AstraZeneca) and its agent, Pfizer, Inc, submitted on February 6, 2015, and as amended July 31, and November 17, 2015, an original new drug application (NDA) 207920, under Section 505(b)(2) of the Federal Food Drug and Cosmetic Act (FD&C Act). The sponsor proposes to market a delayed-release tablet form of the proton pump inhibitor (PPI) esomeprazole 20 mg as an over-the-counter (OTC) product for the treatment of frequent heartburn (occurring 2 or more times per week) in adults 18 years of age and older. The October 23, 2015 labeling review discusses the February 6 and July 31, 2015, labeling submissions, and includes labeling recommendations that were communicated to the sponsor on November 3, 2015. This review, the second of two, amends our October 23, 2015 labeling

Reference ID: 3848998

Labeling Review NDA 207920 Page 2

review. This is a review of the labeling submitted November 17, 2015 compared to the labeling reviewed on October 23, 2015.

II. REVIEWER'S COMMENTS

A. 2-, 14-, 28-, 42-count and 42-count “Club” cartons

i. Outer Carton Label Outside Drug Facts

Principal Display Panel

a. Below the “Nexium” section of the proprietary name and to the left of the “24HR” section of the proprietary name appears the statement “esomeprazole delayed-release tablets 20 mg/Acid Reducer” as requested in November 3, 2015 labeling comments. Comment: The change is an accurate statement of the established name and dose as per the Cross-Discipline Team Leader review dated November 5, 2015, and is acceptable.

b. The statement is removed from all labeling as agreed in

the July 31, 2015, amendment by the sponsor.

Comment: This is acceptable.

Submitted Labeling Representative of Following SKUs

Submission date/replaces

2-count immediate container (bottle)

N/A November 17, 2015, replaces February 6, 2015

2-count sample carton N/A November 17, 2015, replaces February 6, 2015



14-count carton N/A November 17, 2015, replaces July 31, 2015

28-count carton N/A November 17, 2015, replaces February 6, 2015

42-count carton N/A November 17, 2015, replaces February 6, 2015

42-count “Club” carton with backer card



(b) (4)


ii. Outer Carton Drug Facts Label

a. Directions

The Directions section on the revised labeling is identical to the approved Drug Facts label (DFL) for the Nexium capsule. During labeling negotiations, the FDA agreed that this section should be the same as the reference listed drug. For details, refer to the Director’s Summary. Comment: This is acceptable.

b. Other Information

The storage statement on the third bullet is revised to read “Store at 20°C - 25°C (68° - 77°F) as recommended in the CMC review. The bullet regarding

is removed. Comment: These changes reflect the labeling recommendations of CMC and are acceptable.

c. Questions or comments?

The “call toll-free 1-866-226-1600” statement is revised to read “call toll-free: weekdays 9AM to 5PM EST at 1-866-226-1600” in response to our November 3, 2015 labeling recommendation. Comment: This is acceptable.

d. Other Sections/Issues For all carton sizes, the DFL specifications comply with 21CFR 201.66(d). Comment: This is acceptable.

During labeling negotiations, the sponsor explained that the approved 2-ct capsule carton format cannot be used for the 2-ct tablet carton as the carton size is smaller for the tablet product. As agreed to in the November 8, 2015 email,

on the carton is eliminated and the “KEEP CARTON FOR COMPLETE WARNINGS AND IMPORTANT INFORMATION” boxed statement and the DFL begins on the carton itself, up to the Pregnancy/breastfeeding warning. The remainder of the DFL and “Tips for Managing Heartburn” is on the peel-back label. The peel-back section of the label still consists of 5 panels:

Panel #1 is the top panel, which contains the “Keep out of reach of children” warning and “Directions”. The top panel has a “LIFT HERE” instruction on the lower right corner and a directional arrow that complies with 21CFR 201.66(d).

Panel #2 and #3 appear when the peel-back label is lifted according to the directions. These panels contain the remainder of the DFL content.


(b) (4)

(b) (4)

(b) (4)

(b) (4)


Panel #4 and #5 appear when the second peel-back label is lifted, and panel #5 is fixed to the carton. Panel #4 contains the “Tips for Managing Heartburn” information, and panel #5 contains the Nexium 24HR logo.


iii. Immediate Container (2- and 14-count bottle) Label The statement of identity on the top face of the “peel-back” type label now reads

“esomeprazole delayed-release tablets 20 mg”. See Section II.A.i.a. for details. The DFL on the remaining two panels conform to the changes described in

Section II.A.ii.b and c. Comment: These changes are all acceptable.

III. RECOMMENDATIONS

Issue an APPROVAL letter to the sponsor for the submitted Nexium 24HR delayed release tablet labeling and request final printed labeling. The final printed labeling (FPL) must be identical to the labeling submitted on November 17, 2015, as follows: 2-count immediate container (bottle), 2-count sample carton, 14-count immediate container (bottle), 14-, 28- and 42-count carton labels and 42-count “Club” carton with backer card label. Please remind the sponsor to delete the “New” graphic after six months of marketing.

IV. SUBMITTED LABELING The labels on the remaining pages of this labeling review were submitted and were evaluated in this labeling review:


8 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page

---------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signedelectronically and this page is the manifestation of the electronicsignature.---------------------------------------------------------------------------------------------------------/s/----------------------------------------------------

MARY R VIENNA11/19/2015

RUTH E SCROGGS11/19/2015


Labeling Review for Nexium24HR

Delayed-Release Tablets Draft Labeling

SUBMISSION DATES: February 6, 2015

July 31, 2015 NDA/SUBMISSION TYPE: 207920 ACTIVE INGREDIENTS: Esomeprazole 20 mg DOSAGE FORM Delayed-release tablet SPONSOR: Pfizer, Inc.

Christine Chirdo Director, U.S. Regulatory Strategy Category Lead 973-660-5602

REVIEWER: Mary R. Vienna, RN, MHA, DNRD, ODE IV TEAM LEADER: Steven Adah, Ph.D., DNRD, ODE IV ASSOCIATE DIRECTOR for LABELING REGULATORY PROJECT MANAGER

Ruth E. Scroggs, PharmD, DNRD, ODE IV Jeff Buchanan, Project Manager, DNCE, ODE IV

I. BACKGROUND AstraZeneca LP (AstraZeneca) and its agent, Pfizer, Inc, submitted on February 6, 2015, and as amended July 31, 2015, an original new drug application (NDA) 207920, under Section 505(b)(2) of the Federal Food Drug and Cosmetic Act (FD&C Act). The sponsor proposes to market a delayed-release tablet form of the proton pump inhibitor (PPI) esomeprazole magnesium 22.3 mg as an over-the-counter (OTC) product for the treatment of frequent heartburn (occurring 2 or more times per week) in adults 18 years of age and older. The delayed-release capsule form of esomeprazole magnesium 22.3 mg is currently approved as an OTC product in NDA 204655 (Nexium® 24HR), and is the reference listed drug (RLD) for this application.



AstraZeneca requested Agency approval of the proposed OTC proprietary trade name Nexium24HR. The Division of Medication Error Prevention and Analysis (DMEPA) reviewed the proposed proprietary name and concluded that it was conditionally acceptable in their April 14, 2015 communication to the sponsor. An information request (IR) was sent to the sponsor on March 25, 2015, requesting an exact-size model of the proposed 2-count sample carton with a peel-back Drug Facts label. The sponsor shipped a sample carton directly to the project manager on March 31, 2015, but did not officially respond to the IR with a submission to the application until July 31, 2015. An IR was sent to the sponsor on July 16, 2015, requesting 3 tablets of the to-be-marketed tablet and data to support the labeling claim The sponsor responded to the IR on July 31, 2015, with a shipment of the requested tablets and a revised label for the 14-ct carton that removes the statement from the label. The submitted labeling is compared to the most recently approved labeling of the RLD for this application, Nexium 24HR capsules (NDA 204655, S-002).

II. REVIEWER'S COMMENTS

A. 2-, 14-, 28- and 42-count cartons

i. Outer Carton Label Outside Drug Facts

Principal Display Panel

a. The principal display panel’s (PDP’s) upper left corner has a blue oval, with the statement “New” in white font.

Submitted Labeling Representative of Following SKUs

Submission date/replaces


N/A February 6, 2015

2-count sample carton N/A February 6, 2015



14-count carton N/A February 6, 2015 Revised July 31, 2015

28-count carton N/A February 6, 2015

42-count carton N/A February 6, 2015

42-count “club” carton with backer card



(b) (4)

(b) (4)


Comment: This is acceptable. Please remind the sponsor to delete the “New” graphic after six months of marketing.

b. Across the top center portion of the PDP is the statement “Treats Frequent Heartburn”. Comment: This statement is a true statement of the “Uses” section of the Drug

Facts label and is acceptable. c. The proposed proprietary name “Nexium 24HR” is located on the purple oval

graphic at the center of the PDP. Comment: From an IDS perspective, the proposed proprietary name is

acceptable. The proprietary name itself is conditionally acceptable (see DMEPA’s letter of April 14, 2015).

d. The PDP has a yellow background with purple edging in the lower left corners. In

the PDP’s center is a large graphic of a solid purple oval shape with a gold double band outline. This graphic is identical to the approved graphic for the Nexium 24HR capsule. Comment: This is identical to the RLD label and is acceptable.

e. Below the “Nexium” section of the proprietary name and to the left of the “24HR” section of the proprietary name appears the statement “Esomeprazole Delayed-release Tablets mg/Acid Reducer” that is identical in size and prominence to the approved label for the capsule product (NDA 204655). Comment: The prominence of the established name is identical to the RLD label and is acceptable. The correct established name and dose itself will be determined by CMC review and labeling discussions.

f. For the 14-, 28-, and 42-count cartons, the statement “May take 1 to 4 days for full effect” appears below the purple oval graphic. For the 2-count sample carton, this statement appears on the lower left portion of the PDP, and the statement “SAMPLE – NOT FOR SALE” appears above it. Comment: These statements are identical to the statements on the approved labeling for the capsule product and are acceptable.

g. For the 14-, 28- and 42-count cartons, the word “TABLETS” and the image of the tablet appears below the statement “May take 1 to 4 days for full effect.” For the 2-ct sample carton, only the tablet graphic appears to the right of this statement. The June 14, 2015, label review from the DMEPA recommended that the agency ensure that the tablet image “represents a true depiction of the actual tablet, reflecting the true tablet imprint, size and color.” In response to our July 16, 2015, communication requesting 3 tablets of the to-be-marketed tablet, the sponsor submitted a 14-ct bottle of the tablets on July 31, 2015. This was compared to the image on the 2-ct model carton and other labeling.

Comment: The proposed tablet image represents a true depiction of the actual tablet in regards to tablet imprint, size and color, and is therefore acceptable.


(b) (4)

(b) (4)


However the tablet is imprinted with 20mg as the dose, which reflects the active ingredient dosage, but not the reflected on the PDP. The correct established name and dose itself will be determined by CMC review and labeling discussions.

h. The declaration of net quantity of contents appears inside the dark purple edging of

the lower left section of the PDP. Comment: This is acceptable.

i. For the 2-count sample carton, the statement “First two doses of a 14-day course of

treatment” appears below the declaration of net quantity. The font size of the statement appears to be identical to the approved 2-ct sample carton for the capsule product.


j. For the 14-count carton label, the statement “One 14-day course of treatment” appears underneath the declaration of net quantity. For the 28-count carton label, the statement “Two 14-day courses of treatment” appears underneath the declaration of net quantity. For the 42-count carton label, the statement “Three 14-day courses of treatment” appears underneath the declaration of net quantity. Comment: This is acceptable.

k. The top flaps of the 14-, 28- and 42-count cartons display the proposed proprietary

name “Nexium 24HR and the statement “Clinically Proven to Treat Frequent Heartburn” divided by two vertical graphic bars in the center. The top flap of the 2-count carton label Comment: This is acceptable.

l. The statement appears in font on the upper right hand corner of the 2-count carton PDP and top flap, and on the upper right hand corner of the top flap of the 14-, 28- and 42-count cartons. An information request was sent to the sponsor on July 16, 2015, requesting data to support the

claim. The sponsor responded on July 31, 2015, with a representative 14-count carton label that removed the claim.

Comment: The revision to delete the statement is acceptable. The sponsor must submit this revision for all labels.

m. Tamper-evident feature statement:

The right side panel’s bottom margin displays the tamper-evident feature statement “Do Not Use if seal under bottle cap imprinted with “SEALED for YOUR PROTECTION” is broken or missing” in dark purple, bolded print for the 14-, 28, and 42-count cartons. The statement appears in a similar font size and color on the left side panel of the 2-count sample carton. Comment: This is acceptable.


(b) (4)

(b) (4)

(b) (4)

(b) (4)

(b) (4)


n. The right side panels of the 14-, 28- and 42-count cartons display a graphic of the 14-count immediate container (bottle), with a statement of the net number of bottles above the bottle graphic. An image of a tablet appears below the bottle, with the statement “ACTUAL SIZE” to the left of the tablet graphic.

Comment: This is identical to the approved capsule labeling and is acceptable.

o. Left side panel “Tips for Managing Heartburn” appears on the upper portion of the left side

panel for the 14-, 28- and 42-ct cartons. The same information appears on the top flap of the 2-ct sample carton. Comment: This is acceptable.

The left side-panel for the 2-, 14-, 28- and 42-count cartons displays the manufacturing information:

Marketed by: Pfizer, Madison, NJ 07940 USA 2015 Pfizer Inc.

Comment: This is acceptable. Below the manufacturing information is the country of origin statement:

“Made in France” Comment: This is acceptable in accordance with 19 CFR 102, Rules of Origin. The content of the statement will rely on the findings of the CMC review.

Below the country of origin statement appears the statements:

“For most recent product information, visit www.Nexium24HR.com” and “Nexium is a registered trademark of AstraZeneca AB and is used under license.”


p. Carton back : The boxed statement “KEEP CARTON FOR COMPLETE WARNINGS

AND IMPORTANT INFORMATION” is in bolded font above the Drug Facts label on all cartons. Comment: This is acceptable.

ii. Outer Carton Drug Facts Label

The Drug Facts Label (DFL) on each label has identical content regardless of count size. The different sections include the following:

a. Active ingredient (in each capsule): “Esomeprazole 20 mg (each delayed release

tablet corresponds to 22.3mg esomeprazole magnesium trihydrate).”



Comment: This is identical to the Nexium capsule DFL (RLD) and is acceptable.

b. Purpose: “Acid reducer”

Comment: This is acceptable as required under 21 CFR 201.66(d)(1).

c. Uses: treats frequent heartburn (occurs 2 or more days a week) not intended for immediate relief of heartburn; this drug may take 1 to 4 days

for full effect Comment: This is identical to the Nexium capsule DFL and is acceptable.

d. Warnings

1. Other warnings: “Allergy alert: Do not use if you are allergic to esomeprazole”

Comment: This warning complies with 21CFR 201.66(c)(5)(ii)(B) and is acceptable.

2. “Do not use” trouble or pain swallowing food, vomiting with blood, or

bloody or black stools.

heartburn with lightheadedness, sweating or dizziness chest pain or shoulder pain with shortness of breath; sweating; pain

spreading to arms, neck or shoulders; or lightheadedness frequent chest pain These may be signs of a serious condition. See your doctor.

Comment: This warning is identical to the most recently approved warning for the Nexium capsule and is acceptable.

3. “Ask a doctor before use if you have” had heartburn over 3 months. This may be a sign of a more serious

condition. frequent wheezing, particularly with heartburn unexplained weight loss nausea or vomiting stomach pain Comment: This warning is identical to the most recently approved warning for the Nexium capsule and is acceptable.

4. “Ask a doctor or pharmacist before use if you are taking”: warfarin, clopidogrel or cilostazole (blood-thinning medicines) prescription antifungal or anti-yeast medicines


(b) (4)

(b) (4)

(b) (4)


b. Across the top center portion of the PDP is the statement “Treats Frequent Heartburn” Comment: This is acceptable. c. The proposed proprietary name “Nexium 24HR” is located on the large capsule graphic at the center of the PDP. Comment: From an IDS perspective, the proposed proprietary name is

acceptable. The proprietary name itself is conditionally acceptable (see DMEPA letter of April 15, 2015).

d. PDP has yellow background with purple edging on upper right and lower left corner. In the center of the PDP is a large graphic of a solid purple oval shape with a gold double band outline. Comment: This is acceptable.

e. Below the “Nexium” and to the left of the “24HR” section of the proprietary

name appears the statement “Esomeprazole Delayed-release mg/Acid Reducer” that is identical in size and prominence to the approved

label for the capsule product (NDA 204655). Comment: See Section II.A.i.e. f. Under the capsule graphic appears the statement “May take 1 to 4 days for full

effect”. Comment: This is acceptable.

g. The statement appears in font on the upper right corner of the PDP. An information request was sent to the sponsor on July 16, 2015, requesting data to support the claim. The sponsor responded on July 31, 2015, with a representative 14-count carton label that removed the claim.

Comment: See Section II.A.i.l. h. The graphic image of a purple tablet appears on the upper right portion of the

PDP, above the “Treats Frequent Heartburn” statement. Comment: This is acceptable. See Section II.A.i.g.

i. The statement “3 Pack” appears in purple font on the left side of the PDP, above the cut-out for the bottle display. Comment: This statement is truthful and acceptable.

j. The declaration of net quantity of contents appears inside the dark purple edging of the lower right section of the PDP.



(b) (4)

(b) (4)

(b) (4)

(b) (4)

(b) (4)

(b) (4)


k. The statement “Three 14-day courses of treatment” appears underneath the declaration of net quantity.

Comment: This is acceptable. See Section II.A.i.j. l. Card back:

The back card label displays the tamper-evident feature statement “Do Not Use if seal under bottle cap imprinted with “SEALED for YOUR PROTECTION” is broken or missing” on the top of the backer card. The appearance of this statement is identical to the approved 42-ct “club” carton for NDA 204655.


The Nexium graphic identical to the one described in Section II.B.i.c-e appears beneath the tamper-evident feature statement, with “Tips for Managing Heartburn” placed to the left of the graphic. Comment: This is acceptable.

The statement “KEEP CARD FOR COMPLETE WARNINGS AND IMPORTANT INFORMATION” is in bold letters against a white background immediately above the Drug Facts label. Comment: This is acceptable.

The manufacturing information appears below the Drug Facts label:

Marketed by: Pfizer, Madison, NJ 07940 USA 2015 Pfizer Inc. Comment: This is acceptable.

Below the manufacturing information is the country of origin statement: “Made in France”

Comment: This is acceptable in accordance with 19 CFR 102, Rules of Origin. The content of the statement will rely on the findings of the CMC review.

Below the country of origin statement appears the statements:

“For most recent product information, visit www.Nexium24HR.com” and “Nexium is a registered trademark of AstraZeneca AB and is used under license.”


ii. Outer Carton Drug Facts Label See Section II.A.ii.

iii. Immediate Container (2- and 14-count bottle) Label The “peel-back” type label for both bottles is divided into three panels, identified by the firm as:



a. Top (face) – This is the panel visible to the consumer before the Top panel is peeled back and displays non-Drug Facts information b. Top (back) – This is the backside of the top panel and displays part of the Drug Facts label content. It is hinged to connect directly to the “Base” panel so that the text continues onto the Base panel. c. Base – This panel continues the Drug Facts content and is affixed directly to the bottle.

a. Top (face) panel

The statement “Treats Frequent Heartburn” appears at the top of the front side of the panel. Comment: This statement is a true statement of the “Uses” section of the Drug Facts label and is acceptable.

The top panel center has a yellow background with purple edging on upper right

and lower left corner. In the center of the top panel is the proposed proprietary name and large graphic described in Section II.A.i.c and d. Comment: This is acceptable.

The statement of identity “Esomeprazole Delayed-release Tablets

mg/Acid Reducer appears on the capsule graphic. Comment: See Section II.A.i.e.

Under the capsule graphic appears the statement “May take 1 to 4 days for full

effect.” Below this statement is the declaration of net quantity of contents, which reads: “2

TABLETS” or “14 TABLETS” for each respective immediate container count. For the 14-ct immediate container, the statement “One 14-day course of

treatment” appears at the bottom margin of the top panel’s front side. The statement “SAMPLE – NOT FOR SALE” appears on the 2-ct immediate container.

In the upper right corner is the boxed statement “KEEP CARTON FOR COMPLETE WARNINGS AND IMPORTANT INFORMATION”.

In the lower right corner is the direction to “LIFT HERE For More Information” followed by an arrow.

The tamper-evident feature statement “Do Not Use if seal under bottle imprinted with “SEALED for YOUR PROTECTION” is broken or missing.

The manufacturer’s address information, country of origin and website for product information appears below the tamper-evident feature statement. Comment: These are all acceptable.

b. Top (back) panel

The unformatted Drug Facts label content found under the Active ingredient, Purpose, Uses headings, and the Warnings through to drug-drug interactions subheading is found on the Top-back panel (i.e., backside of the top panel). A directional arrow leads the reader to the adjacent base panel.


(b) (4)

(b) (4)


Comment: See Section II.A.ii. c. Base panel

The base panel continues the unformatted Drug Facts label content from the Top (back) panel with the remainder of the Warnings drug-drug interactions subheading, “Stop use and ask a doctor if, pregnancy breast-feeding and Keep out of reach of children warnings. It includes Directions and Other Information (storage statement), “Keep the carton…” and Questions and comments. The inactive ingredients are not listed on the immediate container labels and are not required to be as they are listed on the cartons.

Comment: See Section II.A.ii.

III. RECOMMENDATIONS Please communicate the following to the sponsor:

A. The following revisions are to be made by the sponsor:

i. Non Drug Facts Labeling

a. Revise the established name and dose in accordance with the CMC review and labeling discussions, where it appears on the carton and immediate container labels.

b. Configure the 2-ct carton to include the full Drug Facts Label on the carton similar to the configuration approved for NDA 204655.

ii. Drug Facts Label a. Directions section, “14-Day Course of Treatment,” first bullet: revise the

statement “swallow 1 tablet with a glass of water before eating in the morning” to “swallow 1 tablet with a glass of water at least one hour before eating in the morning” to reflect the clin/pharm review findings.

b. Other Information section, third bullet: revise the storage statement to reflect the recommendations of the CMC review.

c. Other Information section, fourth bullet, “[bullet] provide a rationale for the deviation

from the Nexium capsule label or remove the statement.

B. We also recommend that the sponsor make the following revisions: i. Drug Facts label:

a. Questions or comments section: include the time that the toll-free number is in operation.

In addition to the changes listed under III. Recommendations, remind the sponsor to submit all labeling with the statement removed to reflect the July 31, 2015 amendment to the application.


(b) (4)

(b) (4)


IV. SUBMITTED LABELING The labels on the remaining pages of this labeling review were submitted and were evaluated in this labeling review:


8 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page


MARY R VIENNA10/23/2015

RUTH E SCROGGS10/23/2015


1

LABEL AND LABELING REVIEW

Division of Medication Error Prevention and Analysis (DMEPA) Office of Medication Error Prevention and Risk Management (OMEPRM)

Office of Surveillance and Epidemiology (OSE)

Center for Drug Evaluation and Research (CDER)

*** This document contains proprietary information that cannot be released to the public***

Date of This Review: June 19, 2015

Requesting Office or Division: Division of Nonprescription Drug Products (DNDP)

Application Type and Number: NDA 207920

Product Name and Strength: Nexium 24HR (Esomeprazole Magnesium) Delayed-Release Tablets, 22.3 mg

Product Type: Single Ingredient Product

Rx or OTC: OTC

Applicant/Sponsor Name: Pfizer Inc. (On behalf of AstraZeneca)

Submission Date: February 6, 2105

OSE RCM #: 2015-430

DMEPA Primary Reviewer: Grace P. Jones, PharmD, BCPS

DMEPA Team Leader: Chi-Ming (Alice) Tu, PharmD


4

4.1 RECOMMENDATIONS FOR PFIZER (ON BEHALF OF ASTRAZENECA)

We recommend the following be implemented prior to approval of this NDA:

A. Carton Labeling

a. Ensure that the image of the tablet throughout all carton bottle sizes represents

a true depiction of the actual tablet, reflecting the true tablet imprint, size and

color.


5

APPENDICES: METHODS & RESULTS FOR EACH MATERIALS REVIEWED

APPENDIX A. PRODUCT INFORMATION/PRESCRIBING INFORMATIONTable 2 presents relevant product information for Nexium 24HR that Pfizer submitted on

February 6, 2105.

Proposed Drug Facts Label for Nexium 24HR:

How supplied: bottles containing 2 tablets (sample) and 14 tablets. Outer carton

contains 1, 2, or 3 bottles for a total of 14, 28, or 42 capsules.


(b) (4)

6

Container and Closure System: bottle contains a seal under the bottle cap that is

imprinted with “Sealed for Your Protection”


7

APPENDIX B. PREVIOUS DMEPA REVIEWSB.1 Methods

On June 8, 2015, we searched the L:drive and AIMS using the terms, Nexium 24HR to identify reviews previously performed by DMEPA.

B.2 ResultsOur search identified one previous review1, and we confirmed that our previous recommendations were implemented or considered.

1 Tu, C. Label and Labeling Review for Nexium 24HR NDA 204655. Silver Spring (MD): FDA, CDER, OSE, DMEPA (US); 2014 JAN 07. RCM No.: 2013-1563.



GRACE JONES06/19/2015

CHI-MING TU06/19/2015



SHILA S NKAH05/26/2015



ANDREW J SHIBER04/27/2015


Version: 12/09/2014

12

Nonclinical (Pharmacology/Toxicology)

Reviewer:

Wafa Harrouk Y

TL:

Paul Brown N

Statistics (carcinogenicity)

Reviewer:

TL:

Immunogenicity (assay/assay validation) (for protein/peptide products only)

Reviewer:

TL:

Product Quality (CMC)

Reviewer:

TL:

Swapan De Y

Biopharmaceutics Reviewer

Peng Duan Y

TL:

Tien Mien Chen Y

Quality Microbiology Reviewer:

TL:

CMC Labeling Review Reviewer:

TL:

Facility Review/Inspection Reviewer:

TL:

OSE/DMEPA (proprietary name, carton/container labels))

Reviewer:

Grace Jones Y

TL:

Chi Ming Tu N

OSE/DRISK (REMS) Reviewer:

TL:

OC/OSI/DSC/PMSB (REMS) Reviewer:

TL:


Version: 12/09/2014

14

• Advisory Committee Meeting needed? Comments:

If no, for an NME NDA or original BLA, include the reason. For example:

o this drug/biologic is not the first in its class o the clinical study design was acceptable o the application did not raise significant safety

or efficacy issues o the application did not raise significant public

health questions on the role of the drug/biologic in the diagnosis, cure, mitigation, treatment or prevention of a disease

YES Date if known:

NO To be determined

Reason:

• If the application is affected by the AIP, has the division made a recommendation regarding whether or not an exception to the AIP should be granted to permit review based on medical necessity or public health significance?

Comments:

Not Applicable YES NO

CONTROLLED SUBSTANCE STAFF • Abuse Liability/Potential Comments:

Not Applicable FILE REFUSE TO FILE

Review issues for 74-day letter

CLINICAL MICROBIOLOGY Comments:



CLINICAL PHARMACOLOGY Comments:



• Clinical pharmacology study site(s) inspections(s) needed?

YES NO

BIOSTATISTICS



Version: 12/09/2014

15

Comments:


NONCLINICAL (PHARMACOLOGY/TOXICOLOGY) Comments:



IMMUNOGENICITY (protein/peptide products only) Comments:



PRODUCT QUALITY (CMC) Comments:



New Molecular Entity (NDAs only) • Is the product an NME?

YES NO

Environmental Assessment • Categorical exclusion for environmental assessment

(EA) requested? If no, was a complete EA submitted?

If EA submitted, consulted to EA officer (OPS)?

Comments:

YES NO

YES NO

YES NO

Quality Microbiology • Was the Microbiology Team consulted for validation

of sterilization? Comments:

Not Applicable

YES NO


Version: 12/09/2014

16

Facility Inspection • Establishment(s) ready for inspection? Establishment Evaluation Request (EER/TBP-EER)

submitted to OMPQ?

Comments:

Not Applicable

YES NO

YES NO

Facility/Microbiology Review (BLAs only) Comments:



CMC Labeling Review Comments:


APPLICATIONS IN THE PROGRAM (PDUFA V) (NME NDAs/Original BLAs) • Were there agreements made at the application’s

pre-submission meeting (and documented in the minutes) regarding certain late submission components that could be submitted within 30 days after receipt of the original application?

• If so, were the late submission components all

submitted within 30 days?

N/A

YES NO

YES NO

• What late submission components, if any, arrived after 30 days?

• Was the application otherwise complete upon submission, including those applications where there were no agreements regarding late submission components?

YES NO


Version: 12/09/2014

18

• notify sponsor in writing by day 60 (see CST for choices) • notify OMPQ (so facility inspections can be scheduled earlier)

Send review issues/no review issues by day 74

Conduct a PLR format labeling review and include labeling issues in the 74-day letter

Update the PDUFA V DARRTS page (for applications in the Program) Other

Annual review of template by OND ADRAs completed: September 2014



JEFFREY A BUCHANAN04/16/2015


Documents

207920Orig1s000 - Food and Drug Administration · 207920Orig1s000 OTHER REVIEW(S) Labeling Review for ... The October 23, 2015 labeling review discusses the February 6 and July 31,